Heart failure & cardiomyopathiesCross-sectional study
Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3
- Cross-sectional study
- health care population-based
- replication cohorts
Authors' conclusion
BAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN-mediated DCM.
Study context
- Population
- Individuals of European and African genetic ancestry in the Penn Medicine BioBank with whole-exome sequencing (WES) linked to electronic health record (EHR) phenotypes, 2014–2023PMBB
- Participants
- 43,731 individuals
- Exposure
- BAG3 C151R carriers vs noncarriers
- Outcome
- Association of BAG3 coding variation with clinical diagnoses, echocardiographic traits and longitudinal outcomes
Main finding
As reported in the abstract
Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) risk with C151R
Carriers vs NoncarriersOdds ratio (95% CI)
DCM
0.85(0.78–0.92)
HCM
1.59(1.25–2.02)
Observational data: associations, not effects.
Further findings
Median
| Outcome | Carriers | Noncarriers | Estimate | |
|---|---|---|---|---|
| Age at death | 71.8 (IQR 63.1–80.7) | 70.3 (IQR 61.6–79.2) | HR 0.85 (95% CI 0.74–0.96) | |
| Heart transplant · median age at transplant | 56.7 (IQR 46.1–63.1) | 55.6 (IQR 45.2–62.9) | HR 0.81 (95% CI 0.66–0.99) | |
| DCM and HF among truncating TTN variant carriers (subgroup, n = 358) · DCM | OR 0.42 (95% CI 0.24–0.74) | |||
| DCM and HF among truncating TTN variant carriers (subgroup, n = 358) · HF | OR 0.27 (95% CI 0.14–0.50) | |||
| 0.10.31310Ratio (log scale) |
Original publication
Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3. JAMA Cardiol. Published 1 December 2024. doi:10.1001/jamacardio.2024.3547
Summarised from the published abstract; every number is checked against it